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(Stroke. 2003;34:2980.)
© 2003 American Heart Association, Inc.

Original Contributions

Disruption of Gene for Inducible Nitric Oxide Synthase Reduces Progression of Cerebral Aneurysms

From the Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Correspondence to Kazuhiko Nozaki, MD, PhD, Department of Neurosurgery, Kyoto University, Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail noz{at}kuhp.kyoto-u.ac.jp

Background and Purpose— The rupture of a cerebral aneurysm is a major cause of subarachnoid hemorrhage, but the mechanism of its development remains unclear. Inducible nitric oxide synthase (iNOS) is expressed in human and rat cerebral aneurysms, and aminoguanidine, a relatively selective inhibitor of iNOS, can decrease the number of the aneurysms in rats. In this study we applied our new mouse model of cerebral aneurysms to the iNOS gene knockout mice and observed experimental cerebral aneurysms in these animals to elucidate the role of iNOS in the process of cerebral aneurysm formation.

Methods— Eight C57/Bl6 mice and 16 iNOS knockout mice received a cerebral aneurysm induction procedure. Four months after the operation, the mice were killed, their cerebral arteries were dissected, and the region of the bifurcation of the anterior cerebral artery/olfactory artery was examined histologically and immunohistochemically.

Results— No significant difference was seen in the incidence of cerebral aneurysms between iNOS+/+ and iNOS-/- mice. However, the size of advanced cerebral aneurysms and the number of apoptotic smooth muscle cells were significantly greater in iNOS+/+ mice than in iNOS-/- mice.

Conclusions— Inducible NOS is not necessary for the initiation of cerebral aneurysm. However, the results of this study suggest that regulation of iNOS may have therapeutic potential in the prevention of the progression of cerebral aneurysms.

Key Words: animal models • cerebral aneurysm • genetics • nitric oxide synthase

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